Gonadectomy of male mice resulted in a significant increase in GABAA receptor binding in forebrain membranes at GABA concentrations of 100-1000 nM, whereas gonadectomy of female mice resulted in no significant change in such binding. Acute swim stress (3 min swim at 32 degrees C) in gonadectomised female mice resulted in a significant increase in GABAA receptor binding in forebrain membranes at GABA concentrations of 400-1000 nM and in the plasma levels of corticosterone, whereas this stress produced no significant change in such binding or steroid levels in gonadectomised male mice. The surgical stress of sham gonadectomy produced significant increases in GABAA receptor binding in forebrain membranes at GABA concentrations of 100-1000 nM in both sexes, such that the acute swim stress induced increase in GABAA receptor binding in unoperated females is not observed. Hormone replacement studies in swim stressed gonadectomised females indicate that intraperitoneal injection of oestrogen (beta-oestradiol, 10 micrograms) or progesterone (6 alpha-methyl-17 alpha-hydroxy-progesterone acetate, 1 mg) significantly decreased GABAA receptor binding in forebrain membranes at GABA concentrations of 100-1000 nM compared to swim stressed, gonadectomised females injected with the sesame oil vehicle. The injection of a combination of oestrogen (1 microgram) and progesterone (0.1 mg) produced a greater reduction in GABAA receptor binding than the injection of either steroid hormone alone. These results indicate that, in addition to neurosteroids and corticosteroids, gonadal steroids contribute to the modulation of GABAA receptor binding in the brains of male and female mice.